Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer
Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer
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DOI：
10.1016/s0360-3016(01)01630-3
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发表时间：
2001-10-01
影响因子：
7
通讯作者：
Mueller-Klieser, W
中科院分区：
文献类型：
--
作者：
Brizel, DM;Schroeder, T;Mueller-Klieser, W
目的：缺氧使细胞能量生产的平衡向糖酵解方向转移，副产物是乳酸的产生。定量生物发光成像允许在个体肿瘤中定量乳酸浓度。我们评估了预处理肿瘤乳酸浓度和随后的发展转移性疾病的患者与新诊断的头颈cancer.Methods和材料：在活检的原发部位的时间，一个单独的标本，采取和快速冷冻，随后定量乳酸浓度使用荧光素酶生物发光技术。使用显微镜和成像光子计数系统直接记录组织切片内生物发光强度的二维空间分布。将光子强度转换为体积相关组织浓度的分布（μ mol/g湿重）。治疗包括手术和术后放疗或原发性放疗，根据目前的疾病阶段和机构的治疗政策。转移性疾病的后续发展构成了主要的临床endpoint.Results：从40例患者获得的活检34评估。喉是最常见的原发部位（n = 25）。其他部位包括口咽（n = 5）、下咽（n = 3）和口腔（n = 1）。大多数患者（74%）表现为晚期T3或T4原发性肿瘤。19例（54%）患者存在淋巴结受累。中位肿瘤乳酸浓度为7.1 μ mol/g。根据这些值是否低于或高于中位数，将肿瘤分类为具有低或高乳酸盐浓度。存活患者的中位随访时间为27个月。低乳酸浓度肿瘤患者的两年生存率为90%，高乳酸浓度原发灶患者的两年生存率为35%（< 0.0001）。高肿瘤乳酸浓度对2年无转移生存率有不利影响（90% vs. 25%，p < 0.0001）。随后转移的肿瘤的中位乳酸盐浓度为12.9 μ mol/g，而持续无疾病的患者为4.8 μ mol/g（p < 0.005）。乳酸盐浓度与提出T阶段或N stage.Discussion：肿瘤乳酸盐浓度升高与随后发展的淋巴结或远处转移的头颈部癌症患者。这种更具侵袭性的恶性表型可能与缺氧介导的放射抗性和转移相关基因的上调有关。(C)2001 Elsevier Science Inc.
Purpose: Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer.Methods and Materials: At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (mu mol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint.Results: Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 mu mol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (< 0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 mu mol/g vs. 4.8 mu mol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage.Discussion: Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes. (C) 2001 Elsevier Science Inc.